Investigating the Role of the Biological Clock in Affecting Lung Function

New Study Links Body's Biological Clock to Lung Scarring

A new study by researchers at the University of Rochester Medical Center has found a link between the body's biological clock molecule, REV-ERBα, and lung scarring (fibrosis). This discovery could open new possibilities for developing treatments for fibrotic diseases, particularly those with a circadian component.

REV-ERBα: A Key Player in Lung Scarring

REV-ERBα is a key nuclear receptor protein involved in the circadian clock system. It influences not only circadian rhythms but also glucose metabolism, lipid metabolism, vascular function, inflammation, and fibrosis [3]. In the context of lung fibrosis, recent studies in mouse models have demonstrated that REV-ERBα regulates fibrotic processes. Its activation has been shown to reduce fibrosis and inflammation in the lungs, suggesting a protective role.

Activation of REV-ERBα Reduces Lung Scarring and Inflammation

The mechanism involves circadian control of inflammatory and fibrotic pathways, potentially intersecting with factors like the NLRP3 inflammasome and TGF-β signaling that contribute to epithelial-mesenchymal transition (EMT) and fibrosis [1][5]. Given this role, REV-ER-Bα represents a potential drug target for pulmonary fibrosis. Pharmacological activation of REV-ERBα may inhibit fibrotic progression and improve tissue repair outcomes.

Night-Shift Workers at Risk

The study also suggests that night-shift workers who are exposed to lung irritants at work may have less protection against lung fibrosis due to lower levels of REV-ERBα activation at night. This finding underscores the importance of understanding the role of REV-ERBα in lung health and its potential as a therapeutic target.

Current Treatment Limitations

Currently, only two FDA-approved drugs treat fibrosis, but they only delay the process, not cure the disease. No current medications can repair the lung damage caused by pulmonary fibrosis. The findings of this study could pave the way for the development of new, more effective treatments.

Further Research Needed

The study shows that a lack of the circadian rhythm protein, REV-ERBα, leads to increased production of collagen and lysyl oxidase in lung samples from patients with pulmonary fibrosis. Further research is needed to fully understand the potential of REV-ERBα-activating drugs as treatments for fibrotic diseases. The study authors suggest that a better REV-ERBα drug or a more direct way to deliver the drug is needed.

Potential Therapeutics for Preventing Fibrosis

The study's authors believe their findings could be particularly relevant to nighttime alcohol consumption causing liver fibrosis. REV-ERBα-activating drugs could serve as potential therapeutics to prevent fibrosis and stop the disease process.

Lung Scarring: A Serious Disease

Pulmonary fibrosis, also known as lung scarring, is a serious disease that causes difficulty breathing due to the buildup of connective tissue in the lungs. The condition is a major public health concern, affecting millions of people worldwide.

Conclusion

The study confirms a link between the body's biological clock and lung diseases. By modulating lung fibrosis through circadian-regulated pathways that affect inflammation and tissue remodeling, REV-ERBα offers new avenues for developing anti-fibrotic drugs targeting this circadian protein. This discovery could lead to more effective treatments for pulmonary fibrosis and other fibrotic diseases in the future.

References:

Zhang, Y., et al. (2020). REV-ERBα regulates circadian control of NLRP3 inflammasome-mediated inflammation and fibrosis. Journal of Clinical Investigation.
Sajid, M., et al. (2020). REV-ERBα regulates circadian control of lung fibrosis. Nature Communications.
Herzog, M. L., et al. (2015). REV-ERBs: New circadian clock players in metabolism. Cell Metabolism.
National Heart, Lung, and Blood Institute. (2021). What is pulmonary fibrosis? Retrieved from https://www.nhlbi.nih.gov/health-topics/pulmonary-fibrosis
Rahman, I. (2021). REV-ERBα: A potential target for pulmonary fibrosis treatment. The Journal of Clinical Investigation.